text:
About TU Delft
With a history of over 170 years of excellence in research and education, TU Delft has established itself as one of the leading technical universities in Europe, as demonstrated in the yearly world university rankings. TU Delft is positioned no. 17 in the world ranking in the Engineering & Technology subject of the QS ranking in 2015. We have 20.000 students on campus and 600.000 online students who are studying MOOCs. TU Delft is partner in Edx, a collaboration of institutes like Harvard and MIT for online education.
We prepare you for your career and future endeavours by combining the expertise of our world-class academic staff with our advanced learning facilities. Our partnerships with the business community ensure that the knowledge you gain can be applied in the real world. This is why our students choose TU Delft: they find appropriate employment easy or become successful entrepreneurs.
With over 100 nationalities, 25% of our students being international students, we can honestly say that you will become part of a truly international community. And with partnerships with more than thirty universities all over the world and our close links with (inter)national industry, we enable our students to further increase their international experience.
We have 4 English taught bachelor studies, 12 bachelor programmes in Dutch en all our masters (>35) are taught in English.
TU Delft offers three-year Bachelor of Science programmes, focussing on mathematics, mechanics and physics. You will attend lectures and apply what you learn in projects. Right from the start you will be working in a team on assignments under the supervision of lecturers. A test or project concludes the Bachelor programme.
More information? www.campus.tudelft.nl
Undergraduate programmes
TU Delft offers the following Bachelor programmes:
- Aerospace Engineering
- Applied Earth Sciences
- Applied Mathematics
- Applied Physics
- Architecture
- Civil Engineering
- Clinical Technology
- Computer Science
- Electrical Engineering
- Industrial Design Engineering
- Life Science & Technology
- Marine Technology
- Mechanical Engineering
- Molecular Science & Technology
- Nanobiology
- Systems Engineering, Policy Analysis & Management
Master of Science
Master programmes
TU Delft offers some 40 English-language MSc programmes. The programme duration is two years. The first year comprises theoretical study, assignments and laboratory work. The second year is largely devoted to thesis work, which involves participating in one of the university's advanced research or design projects or taking an internship or research assignment within a company.
Problem-oriented, creative, innovative, learning by doing. Our objective is to produce graduates who are critical independent thinkers so they later become engineers capable of independently solving problems. The curriculum focuses to a great extent on analysis and problem-solving in groups, and the writing of papers. During your study, guidance and assistance will be available at all times.
Read more about:
Studying at TU Delft
This website not only offers information about our Master's degree programmes but you can also find out more about Studying at TU Delft. It covers subjects such as study facilities, information activities, admission and application, finances, student life, finding accommodation, and information for international students, for example.
Overview TU Delft's MSc programmes
You can get two different overviews of TU Delft's master's programmes:
- a list of all master's programmes and their associated tracks
- a list of master's programmes by theme
International Student Ambassadors
With over 100 nationalities– 30% of our MSc students and even over 60% of our PhD students– being international students, we can honestly say that you will become part of a truly international community. Curious about what it is like to be an international student at TU Delft? Contact our Student Ambassadors.
Post graduate programmes
- Phd at TU Delft
TU Delft offers a stimulating environment for excellent PhD candidates who wish to obtain a doctoral degree with the highest possible value for their career.
- Traineeships engineering design
The objective of designer programmes is to increase the designer's independence and flexibility and it trains designers to look beyond the limitations of his own discipline.
- Programmes for management and innovation (Executive education)
Executive education Studies offers five major postgraduate programmes. These programmes aim to strengthen the innovative capabilities of individuals and organisations from both the private and the public sector.
- Post-master programme 'Master City Developer'
Erasmus University Rotterdam, Delft University of Technology (Real Estate & Housing) and OBR (the 'Development Company') Rotterdam offer a top-level degree course focusing on employing an integrated approach in the development of urban areas.
- Post-master programme 'European Post-master in Urbanism' (EMU)
Four leading European universities – UPC Barcelona, TU Delft, KU Leuven and Universitá IUAV di Venezia have designed a joint post-master programme 'European Post-master in Urbanism'.
- Post-master programme 'The Berlage Post-master in Architecture and Urban Design'
The Berlage Post-master in Architecture and Urban Design focuses intensively on how architects and urban designers practice in a globalized world, concentrating on the complex development of the built environment within different context.
- Short courses
TU Delft offers a variety of short courses, which enable engineers to keep up with recent developments in their own field.
- Stan Ackermans Institute
- Online education
- Professional Education
Contact and accessibility
TU Delft
+31 (0)15 27 89111
+ 31 (0)6 10339730
Postal addres
Postbus 5
2600 AA Delft
The Netherlands
Information press/media
Search for employees
Find your way to
- Campus map (PDF, 687KB)
- Charging points map (JPG, 877KB)
Name Directory
Work in progress
Road and maintenance works can occur on and around the campus of TU Delft. Read more
Public Transport
The TU Campus can be reached from Delft Station with the district lines 69, 55, 174 or 40.
By Car
The TU Campus is easily accessible by car via the A13, exit Delft/Pijnacker and exit Delft Zuid/TU-wijk.
Housing TU Delft
For more information about the accessibilty of the TU Delft buildings go to the overview.


text:
Street Sports Magazines & Media KitsAdvertising info, sponsorship opportunities and magazine media kits published in Street Sports category.
Topics: Street Sports, Skateboarding, Scootering, Street Luge and more.
National Magazines
TransWorld SKATEboarding has been the largest, most progressive and most respected skateboarding magazine in the world for over 26 years.
Regional & City Magazines
By: Juice Enterprises Inc

subset: commoncrawl


text:
Sing to the mountains, sing to the sea. Raise your voices; lift your hearts. – Dufford. That is what the music program tries to emulate through all music making during services in and outside the church. Our volunteer ensembles are ever growing and making music an integral part of the mass and liturgy at Our Lady of Mount Carmel.
We have an ever growing cantor program which is open to anyone and everyone. Our chapel choir (High School – Adults) sings at the 9am Sunday Mass, but also participates in several other events throughout the year.
The contemporary Ensemble is small right now but continues to grow and with the help of the piano and guitar soloist participates at the 11am Mass. This opens the door to new music and allows the congregation to also hear traditional hymns.
If you are interested in joining one of these ensembles contact the Music director directly at email@example.com


text:
By now you're most likely familiar with the term "shipping". If not, it's the shortened form of "relationship". In the old days we called it "slash" to represent the / in between two character names on fanfiction sites. ("Iron Man/Rainbow Dash erotic honeymoon.") Either way, it's all the same, fantasizing two (or more!) characters linked either romantically or sexually. Recently there's been a new "trend" in ship naming. It's a trend that confused me at first, but I've come to love: "Trash Ship".
The best way I can sum it up is that a trash ship is a ship you KNOW is bad/problematic/unhealthy/wrong and screw it you ship it anyway. The common core, and in my opinion charm, to this is that the shippers and fully cognizant to the unhealthy nature of their ship. Previously this was called "darkfic". Darkfic has been around pretty much since the dawn of fan fiction. It's nothing new, and is a concept often explored to some very terrifying depths. An example of a trash ship would be HYDRA trash party which involves loves of abuse of characters within the Captain America universe.
But it's not just fic. We, as people, have loved dark stories for centuries. The show Hannibal has one of the most intense and dedicated followings. Les Miserables is one of the most successful musicals of all time. Jessica Jones is a wildly successful Netflix show.
It would make sense that the interest carries over into fanworks too. Now discussing the whys of all that motivation is way above my pay grade, and not the point of this article. So what my point, you ask, exhausted with me by now.
Trash shipping is fine. Sometimes even good for you!
(Now that's a blanket statement, and I feel I should cover my butt and say, "Yes there are some situations that are not ok because it's carrying into real life." However this is purely about fan fiction that does not cross to the real world.)
So why am I writing this? Well, for the trash shippers. I, myself, love me some problematic ships. Largely because I love delving into the psychological working of two vehemently opposed forces. It just usually has great storytelling, which I love. However, a rising issue on sites like tumblr (where a tag tracking system is used) is that hate for a ship is being tagged. Now, this happens with all ships, but I see the most damage being done to the trash shippers. People going into these tags and calling the shippers sick, wrong, defective, etc. This is never good for any fandom, no matter what. So I wanted to bring up a few points and maybe you discover your own trash ship in yourself.
Trash shippers, you are NORMAL for liking it. Let me break some things down.
Sigmund Freud theorized that we have two things within us, the "id" which is our instinctual desires, and the "superego" which is our more moral and critical thinking side. These two things do not have to connect for you to enjoy something. It's how Schadenfreude is even a thing. We know we shouldn't enjoy someone's pain, but we do. If we didn't enjoy the darkness the "horror" and "thriller" genres wouldn't even exist. We know enjoying the exploits of a cannibal serial killer is wrong, but we enjoy it because it's a good story. Just like we know we shouldn't enjoy a problematic ship but we do. Heroes and villains have been romantically linked by fans since the dawn of time. Yes I have seen a trash ship of Harry Potter and Voldemort, and that ship is just as valid as any other ship.
But why? It's fucked up? Ya damn right it is, and often that is heavily acknowledged but the shipper themselves. I'm trying to go this whole thing without discussing kink shaming because that's both similar and very different, but for ease, I'll use it here briefly. People who are kink shamed, or ship shamed, rarely experience it once. They are aware their thing is not good. They are aware you hate it. The only thing you're actually accomplishing is hurting another human by abusing them for something that may have very natural motivations; such as coping with a horrific life situation by playing it out a different way.
Entertainment takes us to a "safe place" where darkness can be explored safely.
Is there some kink you've always been intrigued by, but know in reality is too risky so you don't? Ship it and enjoy.
Is there a problematic time in your life and you want to read something to survive the situation through a stronger character? Ship it and enjoy.
Is there a character that reminds you of an abuser so much you hate them, and want to read them getting their comeuppance? Ship it and enjoy.
When we consume dark media, we're running the gamut of "enjoying darkness in a safe place" to "using it as a coping mechanism", and it's all valid. Also, at the core of fandom facts, every ship exists. Everything. You can hate something all you want, but it exists. Then if you add in crossover fics it gets really wild. At the end of the day, a ship you think shouldn't exist will anyway, so what are you actually doing?
Your attacking a person. Not a ship. A person. Everyone has their own reasons for liking something, trivial or deep feelings, and they deserve respect to like their thing in peace. Most people hide it under the guise of worrying about them in real life. That enjoying these things will carry over into real life. But is that really what you think? Or is it that something is so repugnant to you that you lose sight of the fact that there are real humans behind that screen?
It's been proven that more often than not, fantasies do not reflect real life intentions (see the tiresome "Do video games cause violence" debate). Often people are simply fascinated by the dark stories because they're often the most compelling. And let me tell you, you can find more brilliantly written, compelling stories for free online than in a bookstore. Add that level of writing to a problematic pairing and you've got a recipe for some really thrilling storytelling, or simple safe-place kink fulfillment. And it's all valid and perfectly normal. I hate guns, they terrify me, but I love FPS video games. They're fun because they're not real. The same goes for the ships we enjoy.
For example, I personally detest shipping Jessica Jones with Kilgrave for seemingly obvious reasons. However, I have a friend that ships it, and she did convinced me to read ONE fic to at least understand where she's coming from. In interest of fairness, I did. What did I find? Such an amazingly thrilling story that I almost began to ship it myself. It had those common thoughts and tones that come from the BDSM community, and that safe exploration of it even when it's acknowledged as unsafe in reality. I still hate the pair, but I respect the shippers.
I even asked some of the staff here at Ace of Geeks for their trash ships and why they love them. What I found was not people who want these problematic situations in their lives, but a common enjoyment for just good storytelling. Not every story has to be pure to enjoy it. So here's some of the trash that our staff loves:
Buffy/Spike – Buffy the Vampire Slayer – "I think it was that Spike was trying so hard to change for her, but because he was quite literally soulless it was stupidly difficult for him. I liked the fact that it was an evil character who was only capable of evil still trying to do good. I'm a sucker for redemption stories." Also "because they are both pretending to be harder than they are"
Emma/Regina – Once Upon a Time – "Henry already has two Moms! Why can't he just have two Moms!"
Kylo Ren/Rey – Star Wars: The Force Awakens – "There's always something compelling to me about corruption of the hero/redemption of the villain stories. I like both sides of it."
Damian Wayne/Dick Grayson – Batman – "So these kids both have Father issues and it's really satisfying to see how they take the family aspects, their brotherhood as it were, and use it in a relationship bonding way. These two have secrets only they can share with each other. They are the only ones to share each other's experiences. They both handle it in different ways: Grayson is eternally smiling and carefree, and Damian is hardened and violent, from having to grow up too fast. That's what makes them compliment each other in such a good way."
Mal/Ben – Descendants – "Basic reform story. Good boy meets bad girl who's not really bad, and they live happily ever in-the-near-future. I'm a sucker for those stories… lol"
Bruce Wayne/Selena Kyle – Batman – "He saw her for what she was, a broken angel that he wanted to give back flight. She saw him for what he was – strength… protection… yet she was afraid to let herself get attached because she didn't want to get hurt or trapped."
Dean Winchester/Sam Winchester – Supernatural – "Dean was forced to be a parent for his little brother and they have very little other social contact. They literally have only each other for what they've been through and being close and inseparable why wouldn't they develop those kind of feelings? They share a heaven, which is meant for soulmates. They don't have any kind of physical boundaries, always touching, always walking too close. all the signs point to it."
So trash shippers, listen to me. I'm there in the dumpster with you. I've got my champagne and shutter shades on while I read my fourth Kylo Ren/Rey fic of the day. Because why not? This is fiction. That's the point. Fiction is where we are safe to do anything. If it's fiction that makes you feel unsafe, stay away. If it's fiction that makes you feel safe, jump right on in.
The point is we need to start respecting each other. We're all just trying to love what we love, and we need to stop hurting each other in the process. You are a normal human being if what you ship is not what you morally agree with. You are not wrong. You are not broken. If you feel that it raises some red flags within yourself that's totally valid too and worth exploring to understand the why and how.
You are not required to only ship healthy and pure relationships. You might even find it therapeutic to NOT ship healthy ships. As long as we're all aware it's not healthy, and we're respecting each other, then it's a good day in fandom.
Is Lord Baelish/Sansa a fucked up ship? Ya damn right!
Should you respect people who still choose to ship it? YA DAMN RIGHT!
Now go my darlings. Enjoy your trash bins. And if you've got a problematic ship you enjoy, let me know! I would love to hear your thoughts on the ship and your theories for it. Because, if anything, fans are the most creative people on the planet.
Enjoy and let others enjoy.


text:
Question about Microsoft Windows XP Professional
I see the following in the bottom bar of the browser ( IE )
what does it means ? what do I do to correct it ? I think shdoclc.dll is an application file of the windows operating system ( XP Professional, version 2002 Service Pack 2 ) of my computer. All other pages on synthasite.com open properly. However, the links related to site builder or editing the site gives me the above mentioned error when clicked.
Kind regards.
Posted by captsarang on
after going to Start > Run > Type in cmd, hitting ok and then typing ipconfig / all as advised - I did not see the words DNS Servers
I tried resetting through internet options on the control panel but the problem continues.
The problem continues. However, now I tried to work on my project through Mozilla Firefox. It is working fine.
I think the problem was in windows system due to some malacious ware causing shdoclc.dll/dnserror which was not allowing IE to open the 'create new website' link on synthasite.com ( displaying error window 'IE - operation aborted' )
I wonder how these dynamically loaded libraries or dynamic link library ( dll ) file or the windows operating system gets corrupt by adwares, spywares, viruses & trojans affecting Internet Explorer. Is there no builtin protection in Windows or IE to keep such malacious software out of your computer.
Just buying one more software to get rid of viruses & trojans seems to be the only solution at present
Thanks for your efforts. I am still looking for a solution.
Vilaskumar Sarang
Pune, India
No it was not a problem of 404 error message or web page not available. It was giving the following message:
Internet explorer aborting operation
I could finally open the desired pages using Mozilla Firefox browser.
The problem still exists whenever I try to use Internet Explorer.
Thanks for your efforts.
get this message while browsing intgernet.with ie cannot display webpage
This is not a problem on your computer. This message shows because a web page you are trying to reach is not available, and so cannot be opened. In the "old days" this would be called a 404 message - file or page not found.
You did not say what the screen itself said; but I believe it will confirm my diagnosis.
Posted on Dec 28, 2008
It could be a DNS problem.
Goto Start > Run. . . > Type in "cmd" (without the quotes), hit enter or ok.
Type in "ipconfig /all", and look in there besides DNS Servers, if there is not one listed that would be your problem.
If that is not it try Control Panel>internet options>Programs> hit Reset Web Settings
Please tell the results and I will continue to help you the best I can if this is not it.
Posted on Dec 20, 2008
SOURCE: I have freestanding Series 8 dishwasher. Lately during the filling cycle water hammer is occurring. How can this be resolved
Hi there,
Save hours of searching online or wasting money on unnecessary repairs by talking to a 6YA Expert who can help you resolve this issue over the phone in a minute or two.
Best thing about this new service is that you are never placed on hold and get to talk to real repairmen in the US.
Here's a link to this great service
Good luck!
Posted on Jan 02, 2017
Tips for a great answer:
Jan 03, 2016 | Computers & Internet
Sep 28, 2014 | hotmail.com
Aug 30, 2017 | Mozilla Firefox
Go to Control Panel, click Programs (software).
Uninstall "Browser Manager" +
"Bprotector" + "Object Installer" + "Babylon Toolbar
on IE"
Then depending on which browser you use , follow the
relevant steps:
----------------------Firefox ---------------------------
> Open a new Firefox window (website)
> Go to Tools> Options> and go to change your
order, the Home. ( f.e www.google.de)
and click OK.
> Remove the search engine of Babylon by clicking
the small arrow next to the icon of Babylon
> Manage Search Engines
> select Babylon and Remove
> Close Firefox and open again
> write in the address Bar "about:config " and
click Enter
> Write in the search engine "Babylon."
> Click on any 'Babylon' preferences with the right mouse
button and select "Reset"
----------------------------- Chrome
Open Google Chrome and click on the "Customize and control Google Chrome " icon by the right side of the address bar; click on Settings:
Click> Settings , choose the option "Open a
particular page or set of pages."
Click "Set Pages" on page Babylon and delete from
the list.
To change the search engine in Google Chrome, please follow
the instructions below:
Open Google Chrome on the "wrench" icon on the
right side of the address bar, click:
Settings> Under "Search", click
"Manage Search Engines ...".
If you see "Babylon Search" as a standard
(default), select please another search engine as the default from (Google,
Bing, etc.). Only then will you Babylon You can remove by clicking the little
--------------------------------- Internet Explorer (IE)
------------ -------------------------------------
Open your Internet Explorer browser, click on
"Tools", then "Internet Options" and in the section
"Tabs" click on "Settings". It will open a new window, on
the option "When a new tab is opened, open:" in the drop-down menu
please choose "Your first homepage". Then click OK, Apply and OK.
for demonstration feel free to visit our Babylon removal Site:
Nov 21, 2012 | Facebook Social Network
Jun 18, 2012 | Computer-Expert Group Computers & Internet
Jul 17, 2011 | Computers & Internet
Apr 25, 2011 | Computers & Internet
Oct 24, 2010 | Computers & Internet
Mar 17, 2010 | Microsoft Internet Explorer 8
Sep 27, 2008 | Computers & Internet
Mar 05, 2014 | Microsoft Windows XP Professional
Feb 19, 2014 | Microsoft Windows XP Professional
Feb 17, 2014 | Microsoft Windows XP Professional
118 people viewed this question
Usually answered in minutes!
Level 3 Expert
3015 Answers
Level 3 Expert
18425 Answers
Level 3 Expert
2678 Answers
Step 2: Please assign your manual to a product:


text:
"Four years ago, these best friends discovered a hot-tub time machine." So says the narrator at the start of the "Hot Tub Time Machine 2" red-band trailer, which Paramount debuted at Comic-Con on Thursday. No John Cusack this time around -- Adam Scott, briefly glimpsed here, seems to have taken his slot -- but that just means more laughs for Rob Corddry, Craig Robinson and Clark Duke. This NSFW trailer is a riot. People who like funny things should watch it below. "Hot Tub Time Machine 2" comes out on Christmas Day.
Celebrity News & Photos


text:
Africa is a vast land with a myriad of different habitats and the climate can vary depending on where and when you travel, which will have an impact on travel logistics, as well as have an effect on the land and in turn the wildlife. Winters are generally dry with mild days and cold nights, while the summer offers hot days, warm nights and the likelihood of rain. Below one can see an overview of the different times of year to travel, but keep in mind that over such a large expanse of land, it is necessary to understand each destinations climate before planning your safari.
Wet Season (October to April)
- Hot days, warm evenings with good chances of rain, typically in late afternoon thunderstorms.
- Rain season brings about the birthing period, so lots of young mammals around.
- Increased activity of birdlife.
- Due to rainfall game can disperse more through bush and away from waterholes.
- Bush is beautiful and green with plants flowering/fruiting.
- Night drives are more productive.
Dry Season (May to September)
- Dry season, with cold nights and mild day time temperatures. Little chance of rain.
- Vegetation thins out and mammals are easier to see therefore a great time of the year for mammal viewing.
- Wildlife becomes more dependent on the waterholes making mammal viewing simpler.
- Cold temperatures mean insect activity drops considerably and migratory birds migrate out of the area, dropping the overall diversity of the area.
- Safari times start later and end earlier, but day time temperatures are milder offering more wildlife activity throughout the day.
What country and which destinations to travel to?
Africa is a continent of immense diversity, and one could spend a lifetime exploring this content never needing to return to the same destination twice. Each destination will differ hugely from the previous. This can make your initial planning a daunting experience, as every website offers beautiful words and stunning images. It is therefore important to do thorough research or have the right guidance to help in selecting the right destinations.
It is important to ask yourself what it is you are hoping to experience. If it is a specific animal you are really hoping to see, you need to be very selective in travelling to a reserve that will offer you the best opportunity to view this animal in its natural environment. Is there a specific destination you wish to visit, and which camp or lodge will be the right choice.
To get the most up to date answers to these important questions, it is extremely important to get guidance from the right people. This is where your Private Guide can offer a service even before your Safari begins.


text:
We have added the ability to collapse/expand forum categories and widgets on forum home.Dismiss Notice
All Civ avatars are brought back and available for selection in the Avatar Gallery! There are 945 avatars total.Dismiss Notice
To make the site more secure, we have installed SSL certificates and enabled HTTPS for both the main site and forums.Dismiss Notice
- Dismiss Notice
Attention Modders! Please check out this thread about adding resource and linking discussion thread in our new Resource Manager.Dismiss Notice
Forum account upgrades are available for ad-free browsing.Dismiss Notice
Civ3 - Flamand & Thor's Sci-Fi Workshop
Fallout: The Rebirth Of Civilization
(Public) Development forum for Fallout: The Rebirth Of Civilization mod.
- Discussions:
- 10
Latest: Discussion Gojira54, Dec 14, 2015
- Messages:
- 377
Star Trek: the Mod
(Public) Development forum for Star Trek: the Mod for Civ3.
- Discussions:
- 17
Latest: Star Trek Units r16, May 3, 2017
- Messages:
- 200
Thread Display Options


text:
$834 1 bed 3150 Pyramid Park, Lakeland FL, 33805
from $834 1 bed
3150 Pyramid Park, Webster Park North, Lakeland, 33805
Commute to Downtown Lakeland
This apartment is in the Webster Park North neighborhood in Lakeland. Nearby parks include Simpson Park and Joker Marchant Stadium.
Sutton Place has a Walk Score of 51 out of 100. This location is Somewhat Walkable so some errands can be accomplished on foot.
Sutton Place Apartments are located in the heart of Lakeland, just off of I-98. This quiet community offers easy access to all areas of Lakeland. It will be easy for you to make Sutton Place the place you will love to come home to. This is truly ranch-style living at its finest. Our single-story, garden-style North Lakeland apartments feature private entrances and patios for your enjoyment. We offer Studio, 1 & 2 bedroom apartments in Lakeland near Lakeland College of Business.\n\nPerhaps even more important than the walls and windows that make up your apartment at Sutton Place is the close proximity to everything that you want in order to live an active and satisfying life. We boast a convenient location close to fabulous shopping, local restaurants, highways, major Lakeland employers, and easy access to public transportation.\n\nNot only are our North Lakeland apartments affordable, they are also pet friendly, meaning theres room for your entire family. Sutton Place is a tennis balls throw from area parks and trails, which were sure your furry friend will enjoy. We welcome your pets with a pat on the head and a scratch behind the ear. For more information about our pet policy, please contact the leasing office today
Pets allowed:
Owner/manager tools | Report bad listing | From apartmentlist.com
Webster Park North, Lakeland, 33805
Some errands can be accomplished on foot.
Flat as a pancake, good bike lanes.
About your score
Explore how far you can travel by car, bus, bike and foot from Sutton Place.
Sutton Place is in the Webster Park North neighborhood. Webster Park North is the 36th most walkable neighborhood in Lakeland with a neighborhood Walk Score of 23.


text:
(The Southern Term: The Yankee Translation)
1. "That dawg don't hunt": That's not how that works, my friend.
2. "Ah-tell-yew-whut": Listen up, I'm about to make an empty threat.
3. "Bless her heart": The following statement is about to be an absolutely brutal diss towards someone who generally has done nothing to deserve it, like a small child, or a slightly overweight honor student.
4. "Y'all": Direct referral to those individuals within the general vicinity.
5. "Shit fire!": Excrement flames.
6. "Noodlin'": The act of fishing for large catfish using nothing but your fist/ lower arm. Generally, this involves placing your fist in the fishes mouth, causing them to bite down, and dragging them out of the water. Disclaimer: Noodles are in no way involved.
7. "Muddin'": Purposely taking your vehicle out into the wilderness, after an intense rainfall, to drive recklessly through the mud and water that has accumulated in the ground. Often this involved multiple friends, and few seatbelts.
8. "Coke": Pop (Seriously, though, what's up with that? Pop?)
9. "Restroom": Washroom. (Again, though, seriously...)
10. "Sweet Tea": I won't even bother translating this one, you wouldn't even begin to understand what I'm talking about.
Because Larry the Cable Guy is not a fair representation of the South. We do not claim him.
Because we do claim Duck Dynasty.
Because, Seriously, please someone explain how "pop" makes even remote sense?
Because that's just How It Is.
Photo courtesy of Christopher Columbus.


text:
At the MIT Leadership Center, we are deeply committed to leadership development. In partnership with MIT Sloan's degree programs (MBA, MFin, MBAn, EMBA, and Sloan Fellows) we work to ensure that leadership is embedded in the curriculum and part of the overall MIT Sloan experience. In addition, we seek to empower students to discover and develop their unique leadership styles, cultivate a more robust leadership toolkit, and actually put their skills into practice through specialized programing and partnerships with student groups and initiatives.
Leadership Curriculum
The MIT Leadership Center, working in collaboration with Sloan faculty and outside instructors, develops leadership content for Sloan Innovation Period (SIP). We are committed to bringing the most innovative and exciting leadership development content to Sloan.
In addition to SIP, all MBA students must take at least one course designated as fulfilling the leadership elective requirement. These courses include Leadership Lab: Leading Sustainable Systems, Discovering Your Leadership Signature, and EnActing Leadership: Shakespeare and Performance to name a few. Across MIT there are other leadership courses and programs that we encourage students to explore. More information about SIP and the leadership courses can be found on MySloan.
SIP Workshop 'Teaming to Extreme'
SIP Workshop with John Sterman
Action Learning Labs
Beyond curriculum, the MIT Leadership Center offers specialized programing to help students develop and hone their leadership skill set. During orientation leadership themes are tied closely to the mission of the school, especially to principled leadership. Activities and programs like an outdoor experiential team activity held off campus at the Warren Center begin to introduce students to team and group dynamics.
Other programs like MIT Sloan's multi-rater feedback tool and insightful 360-feedback report, the Peer to Peer (P2P) Program which allows second-year MBA students, Sloan Fellows, and EMBAs to serve as Coaches for first year students, and optional leadership workshops all help maximize a student's experience while at Sloan and provide the foundation for ongoing development and growth for personal effectiveness and careers development.
Student Voices
We seek to empower students to discover and develop their unique leadership styles, cultivate a more robust leadership toolkit, and actually put it into practice through partnerships with student groups and initiatives. MIT Sloan students are furthering the conversation on leadership and leaders everyday through their discussions and actions in the classroom, on campus, and in the world at large.


text:
Simple chains, embellishment charms, and stamped tags to compliment and further customize your jewelry.
I've had some questions regarding how I keep the orders straight. Well …
In light of the recent attention surrounding breast milk jewelry please allow …
All prices are in USD.
Copyright 2018 Hollyday.
Sitemap |
Ecommerce Solution by BigCommerce


text:
Swing timing is an important concept in djembe drumming, as it occurs frequently in West African rhythms. It also crops up in Western styles of music like jazz, blues and country. Yee haw!
It is a matter of slightly changing the length of certain notes and shortening the length of others to create a difference in how the rhythm sounds.
In practice this usually means where 2 notes are written with equal time lengths, the first is lengthened slightly and the second is shortened, or vice versa. When you play a series of these pairs of notes you get swing timing, also known as the shuffle.
Try this little exercise to help understand it better:
The 'one-and-a' Exercise
Using one hand, tap each finger on a table, counting to 4:
- index finger on count 1
- the middle finger on 2
- ring finger on 3
- little finger on 4
Do it slowly and count aloud 'One-two-three-four'. When you get to 4 repeat from 1.
Important! Make the transition back to 1 smoothly (i.e. as if you are continuing on to 5).
Now, keep tapping at a nice slow pace, and in between each count, add the words 'and a'. Keep tapping your fingers only on every beat (i.e. don't tap out the 'and a', just say it). Like this:
Important! All the notes are of equal length. In effect, it is one long word: 'oneandatwoandathreeandafouranda'
When you repeat it, it is: 'oneandatwoandathreeandafourandaoneandatwoandathreeandafouranda' etc. Yowser!
On a chart, the beats represented by the words 'and a' are represented by '+' and 'e', like this.
Congratulations, if you understood that, you have a grasp of the concept of triplets. Now to take it a bit further we're going to show you what happens in swing timing.
Swing Timing
Tricky bit ahead! Tap the rhythm again, but this time leave out the 'and', counting 'one a-two a-three a-four'. It is important to leave the space empty where the 'and' used to be (it helps to say the 'and' in your mind).
So without changing the rhythm of the other notes, you end up with:
one (space) a two (space) a three (space) a four (space) a
One a-two a-three a-four
On the chart it looks like this:
To get a better grip on it, and to avoid changing the timing, try adding just the first 'and', to make sure it still sounds the same as before, as shown below.
Viola, you have invented swing timing!
OK, so how does this all relate to African drumming? Well, if you see a chart marked swing, like this:
...in fact it is meant to be played like this:
If you're confused, take heart, read this page again.
Swing Timing is Fluid
While the charts above show the basic concept behind swing timing, in practice the notes are not all exactly the same length. The timing becomes less precise and more fluid.
The length of the notes can also change over the course of the song. This will change the feel of the swing.
It's something that eventually becomes easier to feel. Getting a hang of it is just a matter of practice. When in a drum circle, take the cue of the timing from the leader.
For most people the above explanation is all you need to know.
For now, you're more than ready to learn a few Djembe Rhythms


text:
100% Authentic Vivienne Westwood Sale.Free Shipping & Retun
Product 5/105
Adorned in a sleek leopard pattern in pink, the Avon Bag 7097 comes complemented with a range of Westwood's awareness, detachable pin badges, referencing the Punk movement. Finished with the Anglomania logo and iconic Orb studded to the front in gunmetal, this petite bag features a shoulder strap that can be worn as a belt through two rear loops.
Top flapPush clasp closureAnglomania logo print liningOne internal zip fastening pocketOne internal patch pocketDetachable badgesDetachable adjustable Shoulder strap measures 120cm at maximum extension


text:
Auto Dealers Resist Plan for Plug-In Tax Credits
WASHINGTON—U.S. auto dealers are resisting a White House proposal that would require them to temporarily cover federal tax credits for consumers who purchase plug-in electric cars.
The government currently offers tax credits of up to $7,500 for the purchase of electric vehicles. Consumers claim the credit on their tax returns.
The White House...


text:
Bel Air Foods Market is located in the foothills of the Santa Monica Mountains overlooking the Roscomare Valley. The store is on Roscomare Road, one of the main corollaries that intersects Bel Air, and stands out as the only large-scale commercial presence in the area.
2323 Roscomare Road
Los Angeles, CA 90077
Open weekdays 7 am – 9 pm
weekends 9 am – 8 pm
(310) 472-5010


text:
After several months – was it really back in January that I posted my most recent update in this series? – I picked up "The Elegant Universe" again and kept reading. On page 349 (in my edition), Green talks about how there was a moment where the universe from being opaque to being transparent.
He then goes on to describe the moment of the birth of the universe in terms that make me think about how he talks about black holes in the previous chapter (p 342-344?). I'm not a hundred percent sure why, but this part of the book reminded me a little of those four-axis graphs, with space on one axis and time on the other, and black holes sucking in all information. It brought to mind the image of a God's Eye, or one of those cool graphic design things everybody used to doodle in high school (the nearest I can find via Google Images is the first graph used on this total stranger's blog entry, but imagine four quadrants of that facing one another).
In the part of the book I'm reading now, Greene says this thing I mentioned earlier about how the universe had a moment where we know it went from opaque to when it went to transparent, and then he talks about how a "gas of freely streaming photons" were able to escape outward.
Now it gets interesting. If you remember back to Homework Takeaway #1: Light Ain't Old, you'll remember that photons are light particles.
In other words, if I may be permitted to wax romantic about this for a moment: at the beginning of time and the universe as we know it, there is a precise moment when a burst of photons, i.e. light, began to be emitted out of darkness. In the interest of investigating an age-old metaphor…sounds a little let there be light, doesn't it?
Oh, and also: We are all made of stars.
Physics is awesome.


text:
The Morning Heresy is your daily digest of news and links relevant to the secular and skeptic communities.
After the Australian Broadcasting Company's big exposé on the abuse suffered by women within Christian church communities, church leaders are finally making some noise about taking meaningful action. Julia Baird and Hayley Gleeson report:
The Anglican Primate of Australia, Archbishop Philip Freier, said he supported an unequivocal apology expressed this week by an Anglican priest to victims of domestic abuse in the Church. "I'm hoping that there will be some words of apology to people who have experienced domestic violence and any failure from the Church at our General Synod, coming up in September," the Archbishop said…
As Father Daryl McCullough said in a Facebook post, "If you are one of my parishioners, know that I will listen, I will believe you and I will not dismiss you."
There's a lot more hubbub over KPFA's cancellation of Richard Dawkins' event as more media outlets pick up the story. There are a lot of big names writing in support of Dawkins, and you can see a lot of those messages here. Hemant Mehta described the problem well:
If KPFA and other so-called progressives think [Dawkins is] wrong, they should hear him out and respond in kind. Refusing to hear what he has to say — especially in this situation, when he was going to talk about the beauty of science, for goodness' sake — is the coward's way out.
David Gorski focuses attention on the physicians who are enabling Gwyneth Paltrow and Goop's snake oil peddling, and how they are "punching down" at their critics, looking for easy targets to attack.
Ken Ham sells the Ark Encounter to himself, and then buys it back from himself again.
In a letter to the editor of the Des Moines Register, Robert Cook reminds everyone that, hey, Congress is trying to sneak a knife in the back to the Johnson Amendment:
Without the Johnson Amendment, churches would become black holes for a flood of dark money that can't be tracked. Why give a penny to a super-PAC when rich donors could achieve the same thing passing their money through a church — tax-free, anonymous and untraceable? Super-PACS as we know them today would cease to exist overnight.
Amanda Kooser at CNET explains that the recent UFO sightings over Cornwall were all part of a publicity stunt by the Eden Project, a bunch of greenhouses with exotic plants.
Australia has new vaccination laws, with big fines for preschools and daycare centers admitting unvaccinated kids, and no religious exemptions for parents. And they're working.
There's yet another article with more reasons as to why climate change will get worse more quickly than previously thought. At this point, I'm ready for the Earth to melt into a liquid state sometime next week.
Snopes is in need of financial support, so leave it to overtly-fake-news site The Onion (via the A.V. Club) to make the call to help the site that debunks fake news.
Buffalo Spree reports on some controversy around the restoration of the Buffalo Psychiatric Center, which some actually think is haunted. Who do you check in with about that? Joe Nickell, of course.
Michele Bachmann says of Donald Trump…you know what? Never mind. It's just not worth it.
Quote of the Day:
"The Goldwater Rule" is the ethical guideline that says mental health professionals should not diagnose public figures they haven't actually dealt with personally. According to STAT, the American Psychoanalytic Association is relaxing that rule, because of you know who:
The impetus for the email was "belief in the value of psychoanalytic knowledge in explaining human behavior," said psychoanalytic association past president Dr. Prudence Gourguechon, a psychiatrist in Chicago. "We don't want to prohibit our members from using their knowledge responsibly."
That responsibility is especially great today, she told STAT, "since Trump's behavior is so different from anything we've seen before" in a commander in chief.
An increasing number of psychologists and psychiatrists have denounced the restriction as a "gag rule" and flouted it, with some arguing they have a "duty to warn" the public about what they see as Trump's narcissism, impulsivity, poor attention span, paranoia, and other traits that, they believe, impair his ability to lead.
Photo credit: Jeanne Menjoulet via Foter.com / CC BY
Linking to a story or webpage does not imply endorsement by Paul or CFI. Not every use of quotation marks is ironic or sarcastic, but it often is.
Follow CFI on Twitter: @center4inquiry
Got a tip for the Heresy? Send it to press(at)centerforinquiry.net!
News items that mention political candidates are for informational purposes only and under no circumstances are to be interpreted as statements of endorsement or opposition to any political candidate. CFI is a nonpartisan nonprofit.
The Morning Heresy: "I actually read it." – Hemant Mehta


text:
A new 15,000L Mack WaterCart was delivered to a Major Central Queensland Coal Mine and is our second WaterCart to be installed on this site. This Truck takes our Hire Fleet to a total of 19 vehicles all of which are hard at work in the Australian Open Cut mining sector.
Want to find out more or get a quote?Contact us today


text:
Browse News Archives
Browse News Categories
UpComing Tradeshows
October 17-19, 2018
October 23-26, 2018
China Brew China Beverage 2018
Shanghai, China
November 27-29, 2018
SPS IPC Drives 2018
Nuremberg, Germany
November 2017
A major U.S. cement manufacturer needed to replace the drivetrain components on a large limestone bridge reclaimer at one of its facilities.
Read More
October 2017
An oil drilling company wanted to replace the mechanical (cam over center) clutches on a large number of its pump jacks operating in various oil fields with a new clutch solution. The existing manually operated PTOs required a worker to visit each individual pump jack in order to engage and disengage the drive motor using a lever-actuated cam.
August 2017
A New York-based wire manufacturer needed to improve their control on a wire rewinding system. New wire is wound onto large spools that will be thousands of feet of material (depending on the size of the wire on each spool).
February 2017
A conveyor OEM was looking for a reliable braking solution for a bucket conveyor unit being built for a West Coast dry food manufacturer. Bucket conveyors feature a chain drive containing a series of buckets that pick up material on one side, transport it vertically, and deposit it at another level.
December 2016
A major European manufacturer of power transmission systems for locomotives approached Warner Electric engineers with a request for a customized clutch to integrate with its new hybrid transmission.
Warner Electric
449 Gardner St.
South Beloit, IL 61080 - USA
Phone: 1-800-825-6544Email: firstname.lastname@example.com
Altra Industrial Motion Corp.
ALL Rights Reserved.
Legal, Privacy Policy


text:
So what exactly is Chatter? It's a Facebook rip off that you use for work instead of for personal use (aka no pictures of you at parties, hitting on "friends", posting NSFW stuff). The main "Chatter" page looks just like the Facebook wall with threads, in thread comments, a like and a delete button. You can update your status, view your "People" (aka friends), share links, etc. Take a look at a picture of my "Chatter" page:
Look familiar? I had to blur a few things out like my companies name which appears above my name and my coworkers last name. Aside from the color scheme it pretty much resembles a less advanced version of Facebook.
Additionally you can add profile information, picture, contact information, an about me section, you can connect or "follow" people (twitter-esque), join groups, upload files and download their Adobe-Air powered Chatter Desktop application for easy status updates.
Maybe Facebook needs to offer a special version just for work?


text:
Mima has worked in the radio industry, full-time, for over 13 years - as a presenter, producer and programme controller/content director.
Mima has presented across most time-slots, but the majority of her career to date has been spent in the mid-morning time slot, as she enjoys the relaxed feel after breakfast as people are getting into their day.
Starting off on the evening time slot on talk and music station, Liberty Radio in London, Mima quickly progressed to the daytimes slot there and was then asked to move to Heart FM in Kent. From there, Mima was given an opportunity to help launch a brand new radio station as part of the Kent Messenger Group of radio stations, KMFM. That radio station achieved a 33% audience share in it's first year on air. Mima then progressed to Regional and Network Programme Controller for the whole group of radio stations and continued her show on air throughout.
As featured on BBC, SKY SPORTS, ITV, KMFM, MIX 94.5


text:
KidZone is a free summer day camp program for local children grades K-6. The camp runs Monday through Friday from 9am-12pm throughout the summer. Breakfast and lunch are served daily as well as fun activities and lessons each day. For more information or to register your child, please call 269-344-6119.
Summer Drop In Hours are available from 1-3pm for youth up to age 16. The Community Center and Gym will be open at this time.
We also offer Mission:Literacy and a Digital Learning Program to provide additional educational opportunities for area youth. Mission:Literacy focuses on improving reading skills among students in 1st-5th grade. The Digital Learning Program offers several courses, from financial literacy to African American History all available in a web-based classroom format. Digital Learning is geared for students age 8 and older.
Volunteers are needed to keep this program free and safe for the community. Click Here to apply!


text:
What does learning look like at Premier Kindergarten?
Premier Kindergarten offers an adapted Early Years Foundation Stage Curriculum.
The foundation stage curriculum is organised into six learning areas;
• Personal, social and emotional development:
This involves helping children to develop a positive sense of themselves, and others; to form positive relationships and develop respect for others; develop social skills and learn how to manage their feelings and to have confidence in their own abilities.
• Communication and language;
Involves giving children opportunities to experience a rich language environment; to develop their confidence and skills in expressing themselves; and to speak and listen in a range of situations.
• Mathematical development;
Involves providing children with opportunities to develop and improve their counting, understanding and using numbers, calculating, simple addition and subtraction problems; and to describe shapes, spaces and measures.
• Knowledge and understanding of the world;
Involves guiding children to make sense of their physical world and their community through opportunities to explore, observe and find out about people, places, technology and the environment.
• Physical development;
Premier Kindergarten provides opportunities for young children to keep active and interactive; and to develop their co-ordination, control and movement.
• Expressive arts and design;
At Premier, children are encouraged to share their thoughts, ideas and feelings, through a variety of activities in art, music, movement, dance, role-play, and design and technology.We cater for children of ages between two and a half to five year olds.
We have well trained and qualified staff and provision for enabling environments, both indoor and outdoor to enhance learning.
Our Kindergarten has adequate resources and keeps upgrading these to ensure that we keep up with the ever changing curriculum requirements.
Play is also stressed at the Kindergarten department. Well planned play activities are a key way in which children learn with enjoyment and challenge during the foundation stage.
Our classrooms and outside environments provide variety of spaces, materials and activities geared to promote active exploration and mastery.


text:
I have never been able to afford a "spiritual retreat"; turns out that's a good thing.
Mother Theresa said on how to contribute to world peace, "stay home and love your families". Kudos for "me". I have stuck it out at home without retreating to a more spiritual setting. I was tempted; I passed the test. Unholy relationships of the past are now holy.
What are you retreating from? Look at the split from Love, and mend it. Forget about moving the body from here to there and calling the distance something better than accepting the Atonement Now.


text:
Freelance journalist Edmund Tirbutt has called on his own experience combating a drink problem to produce a book to help others win the battle with alcohol.
Author of Beat the Booze, Kent-based finance journalist Tirbutt said: 'To say that journalists are capable of enjoying a pint or two is probably something of an understatement. During my time in this industry I have come across hundreds of people who my book could really help.
'Most do not perceive themselves as having a drink problem but they are well on the way to developing a serious addiction. It probably hasn't occurred to them that they could be much happier by drinking less or by not drinking at all, and, hopefully, I can help them change their lives."
Tirbutt and his co-author, wife Helen, interviewed alcohol experts and drinkers who have cut down or stopped drinking alcohol altogether. Both authors also called on their personal experiences in combating alcohol. Edmund has been tee-total for the whole of his 21 years in journalism, after overcoming a serious drink problem.
Press Gazette readers can buy the book for £6.49, saving a third on the cover price, by phoning 01730 233870 or going to the website (see right).


text:
Your company name or logo can be put on almost any surface.
Lasting Impressions can create an unlimited variety of custom printed stickers, labels and decals in various sizes which are printed onto high quality self adhesive vinyl that is suitable for both inside and outside use.
We can produce large or small quantities so whether your need labels or decals for property identification, point of sale displays or even identifying your company vehicles, our state of the art technology produces a high quality finish which will help identify and promote your business.


text:
THE IDOLM@STER MILLION LIVE! 4thLIVE Official Key Ring
|Inventory status
(C)BANDAI NAMCO Entertainment Inc.
Item Explanation[ Translate ]
The Official Key Holder that commemorates the holding of "THE IDOLM@STER MILLION LIVE! 4thLIVE TH@NK YOU for SMILE!!" has arrived!
Its acrylic body that looks sparkling and shining features a design using the live logo as motif.
The live holding schedule and venue name are inscribed with foil stamping on the ribbon tag.
Please enjoy it as a 4thLIVE performance commemorating item and also as an accessory to attach on bags and keys.
Product Specifications
Material Body: acrylic / tag: PVC / parts: zinc alloy
Size: Approx. H80 x W 60 mm (body) / approx. W 60 x H 20 mm (tag)
Country of origin: Japan
※ Since shipping takes place only once all items are packed together in the case of an order including other products,
delivery before the performance might not be possible in some cases, so please make sure to check the scheduled delivery date of each item.
※ Please note that products specifications and contents are subject to change without notice.
※ Please order after carefully confirming the item / quantity in the cart to avoid mistakes.


text:
1Streetcar Live: The live music series aboard Tampa's TECO Line Streetcar System returns Saturday. Americana duo Lady and the Bard will play folk, bluegrass and blues for riders from 5 to 7 p.m. Streetcar fare is $2.50 one-way, $5 all day. See tecolinestreetcar.org or catch the trolley at Centennial Park, 1800 E Eighth Ave., Tampa.
2Ciro Guerra: Oscar-nominated director Ciro Guerra will be at Eckerd College this week, with screenings of his films and talk-backs. On Friday, you can see his internationally acclaimed and 2015 Cannes award winner Embrace the Serpent. Shot in black and white, it tells the story of two scientists on the Amazon River in search of a healing plant. Variety called it a "comprehensive critique of the destruction of indigenous cultures at the hands of white invaders." A question and answer session with the director follows the free screening at 7 p.m. Friday at the Eckerd College Dan and Mary Miller Auditorium. Saturday features a deeper discussion with the Colombian director on his career as a filmmaker and his aims as an artist. It is free for the public at 6 p.m. Saturday also at the Miller Auditorium, 4200 54th Ave. S, St. Petersburg.
3Pasco Pet Fest: Bring your well-mannered pooch to the annual festival with food and wine for sale, music, vendors, adoptable pets, auction and a raffle. Benefits the Furbabies Foundation. Free (donations accepted). Florida Estates Winery, 25241 State Road 52, Land O'Lakes. (813) 996-2113. 11 a.m.-3 p.m. Saturday.
4Pinellas Pork Barbecue Cook-Off and Rodeo: Area amateur barbecue chefs cook up pork butts, ribs or both for prizes. Stick around noon-10 p.m. Saturday for a full rodeo with bull riding, live entertainment, beer, bounce houses, children's rides, a bubble runner and fireworks. Free. England Brothers Bandshell Park, 5010 81st Ave. N, Pinellas Park. (727) 369-5747.
5Yes! FAIR: The ninth annual community event for FAIR (Family Abilities Information Rally) 10 a.m.-3 p.m. Saturday will have some 200 exhibitors on disability awareness, education and resources in the community. In addition, there will be singing, dancing, music, a picture with Santa, a bounce house, arts and crafts and more. Food trucks on site. Free. All People's Life Center, 6105 E Sligh Ave., Tampa. (813) 420-7708.


text:
Beneficiile scortisoarei
Beneficiile Scortisoarei Scortisoara este o mirodenie cunoscuta pentru aroma pe
Oakley He moncler jackets regarded each abercrombie
Oakley He moncler jackets regarded each abercrombie and fitch person
documents detail interception of immigrant boat headed toward palm beach county
Looking around, looking around, I can understand it. Finally I
cheap oakleys Over the course of two and a half weeks
62% of people with diabetes are overweight or obese with
musical comedy troupe delights senior citizens at temple beth sholom
fake oakley sunglasses My family helps me do the things
Reliable timing is also essential
Reliable timing is also essential in controlling the instrument. Nothing
People always ask how to mimic her good fortune
People always ask how to mimic her good fortune. "Come
fake oakley sunglasses When it comes to puffiness
Since the global economy began to circle the drain in


text:
Connecting mixed media to make a movement
Hey Cheyenne! Great stuff, I love it! I'm glad you had a great first semester, it will only get more fun! Thanks for stopping in to see me, it was great seeing you, even if it was for a short time. Don't be a stranger! You might want to email me ahead of time, 'cuz they're getting real strict about unannounced visitors.Hope to see you soon!MrB


text:
Advanced Search
↵† These authors contributed equally to this work
↵‡ These authors contributed equally to this work
Overall workflow for the analyses described in the Results section.
Pan‐cancer PCA of copy number data from a balanced, random sampling of tumors of 15 tumor types from The Cancer Genome Atlas (TCGA). The average tumor PC scores for each tumor subtype are shown. Pan‐cancer PC1 scores primarily separate diploid from highly aneuploid tumors, while PC2 distinguished GBM from the other tumor types (Appendix Fig S1A and B). Four tumor subtypes with similar PC scores are labeled as "Signature positive (+)". Tumor type abbreviations are as defined by TCGA: ovarian serous cystadenocarcinoma (OV), breast (BR), bladder urothelial (BL), and thyroid (TH) carcinoma (*CA), uterine corpus endometrial carcinomas (UCEC), lung (LU), and head and neck (HN) squamous carcinomas (*SC), skin cutaneous melanoma (SKCM), lung (LU), rectal (RE), colon (CO), stomach (ST), and prostate (PR) adenocarcinomas (*AD), glioblastoma (GBM), low‐grade glioma (LGG), and kidney renal clear cell carcinoma (KIRC).
Copy number profiles of 873 breast invasive carcinomas (BRCA). Tumors (rows) sorted by tumor‐specific principal component 1 (PC1) score with genomic locations listed across the top. PCA identified and distinguished two signatures with similar degrees of variance in the first component. The triangle marks the transition from signature A through diploid samples to signature B. The membership of each tumor with known molecular subtypes (e.g., basal/luminal) and mutant TP53 status are indicated on the right with red horizontal bars and corresponding permutation‐based enrichment P‐values. Basal and luminal subtype classifications are from a published gene expression‐based determination (The Cancer Genome Atlas Research Network, 2012b). Signature A was moderately enriched for claudin‐low tumors, whereas the HER2‐enriched subtype was not significantly associated with either signature A or B (Fig EV2D). Similar PCA‐based distinctions were observed in the LU, OV, and UCEC datasets (Fig EV2A–C).
Pan‐cancer PC1 loadings and signature A summary profiles for ovarian (OV), breast (BRCA), uterine (UCEC), and lung (LU) tumor types. Summary signatures are normalized gene loci signal‐to‐noise ratios (SNRs) of the top 10% of PC1‐based core signature A tumors compared to normal (non‐tumor) samples. Pan‐cancer PC1‐3 loadings are shown in Appendix Fig S1C. Consistency signatures of conserved amplification and deletions (consistent regions) are indicated by their signed absolute minimum consistency score (SAMCS). The SAMCS is non‐zero when all CNA summary signatures have the same sign across all tumor types, and is derived from the absolute value‐based minimum summary metric, and then re‐signed positive for amplification or negative for deletion (see Materials and Methods). In the bar graph, red and blue denote consistently amplified and deleted regions, respectively. The number or percentage of consistent regions, genome coverage, and gene loci are indicated. The positions of canonical oncogenes, proto‐oncogenes, tumor suppressor genes, and telomerase components (TERC, TERT) present in these regions are indicated.
Breast signature A tumors have more DNA breakpoints per chromosome than signature B tumors, but similar levels of copy number alteration (as measured by an integrated CNA score proportional to the extent and absolute value magnitude of amplifications and deletions). P‐values are indicated (top, Mann–Whitney U‐test; bottom, Student's t‐test), and data presented in box (median, first and third quartiles) and whisker (extreme value) plots. The number of breakpoints is inversely proportional to the mean DNA segment length.
KEGG metabolism pathway enrichment analysis based on consistent CNA patterns in the core signature A tumors of (A). The OV, BRCA, UCEC, and LU signatures from (C) were sequentially added and only directionally consistent CNA changes were retained (see Materials and Methods). The combined glycolysis–gluconeogenesis (glycolysis) and pentose phosphate pathway was included based on our prior mRNA work identifying the predictive value of this gene set (Palaskas et al, 2011). Core glycolysis is a KEGG‐defined gene subset (M00001). Table EV1 lists enrichment results for all KEGG metabolism pathways.
Schematic showing average signal‐to‐noise (SNR) metrics of core glycolysis pathway genes plus 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase (PFKFB and TIGAR), lactate dehydrogenase (LDH), and pyruvate dehydrogenase (PDH) in core signature A tumors from (C) and (E). A more detailed listing of the gene names can be found in Materials and Methods.
Gene copy number alteration distributions of selected glycolysis genes, TIGAR, the tumor suppressor p53, and the p53‐associated cancer genes MDM2 and CDKN2A in BRCA tumors. Data are presented in box (median, first and third quartiles) and whisker (extreme value) plots.
A–C Copy number profiles of 359 lung (LU) squamous carcinomas (LUSC) and 368 lung adenocarcinomas (LUAD) (A), 583 ovarian serous cystadenocarcinoma (OV) (B), and 492 uterine corpus endometrial carcinomas (UCEC) (C) tumors sorted by their PC1 score. Signature A tumors are sorted to the top of the heatmap. PC1‐ranked tumors were analyzed for enrichment of known mutations or molecular subtypes (e.g., basal/luminal in breast, see D for all subtypes tested). The red horizontal bars to the right of each tumor type indicate the tumor subtype (e.g., LUAD), or the presence of the indicated mutation (e.g., TP53). Normalized enrichment score and permutation P‐value for each significantly enriched mutation or clinical subtype are shown below the tick plots.
D. Enrichment analysis of molecular subtypes in PC‐defined signatures A and B. The molecular subtypes tested were defined by the TCGA (The Cancer Genome Atlas Research Network, 2011, 2012a,b, 2013, 2014). Because LUAD and LUSC were combined into a single dataset LU, all LUSC and LUAD subtypes were associated with signatures A and B, respectively. Within LU, signature A was most associated with the classical subtype of LUSC, and signature B was most associated with the bronchioid subtype of LUAD. Permutation‐based P‐values are indicated.
E. Amplification of MDM2 and deletion of CDKN2A are mutually exclusive in signature B human BRCA. Each point represents a single patient sample. Samples are colored red or blue according to their membership in signatures A or B, respectively, with intermediate colors representing intermediate PC1 scores between signatures A and B. Samples colored white represent nearly diploid tumors, as indicated by the triangle in Fig 1B.
Pan‐cancer clustering of 3,037 copy number profiles using a balanced, random sampling of tumors from 15 tumor types. The dendrogram reveals the presence of a cluster containing multiple tumor types and enriched in PCA‐defined signature A tumors (hypergeometric P‐value = 1.1 × 10−70 for concordance between the PCA and hierarchical clustering results). There is also a cluster enriched in the generally less uniform PCA‐defined signature B tumors (hypergeometric P‐value = 4.5 × 10−12), which contains other tumor types as well (e.g., SKCM). In the key, the individual tumor types and pan‐cancer PC1 scores are indicated. Additionally, for the core signature A tumors (OV, BRCA, UCEC, and LU), tumor‐specific subtypes (e.g., BRCA basal and luminal) and tumor type‐specific PC1 scores are indicated. The gene loci CNA levels in the heatmap are ordered based on their chromosomal locations (columns).
Average pathway enrichment signal strength for the top 10 enriched KEGG metabolism pathways based on the consistent CNA patterns across multiple tumor types. The four core CNA signature A patterns are defined as in Fig 1C. CNA signatures for other tissue tumor types are defined by the signal‐to‐noise ratios (SNRs) of all tumors compared to tissue‐matched normal (non‐tumor) samples. Starting with the four core signature A tumor types from Fig 1 (OV, BRCA, UCEC, and LU), additional human (orange) or human and mouse (blue) signatures were sequentially added based on their decreasing tissue type pan‐cancer PC1 score from Fig 1A (see Materials and Methods). The resulting sequentially restricted consistency signatures are illustrated in (D). A maximal peak (indicated by an arrow) in the enrichment signal of this sequential analysis is seen after adding tumors through human HNSC and mouse Coad (no mouse Hnsc signature was available). Enrichment signal strength is based on the negative log frequency of equivalent enrichment by chance (i.e., permutation P‐value). Mouse tumor type abbreviations are shown with lower case letters but otherwise match the human TCGA abbreviations.
Enrichment analysis of metabolism (75 KEGG pathways) and canonical pathways (CP; 1,321 MSigDB canonical pathways). Permutation P‐values for the consistent CNA patterns from the four human core signature A tumors (defined in Fig 1C), the human expanded signature A (from A), and the human expanded signature A combined with corresponding mouse cancer models (from A). FDR calculations are described in Materials and Methods. Tables EV1 and EV2 list all sequential enrichment results for KEGG metabolism and canonical pathways, respectively.
Enrichment score for the glycolysis pathway upon sequential addition of human tumors and mouse models (as in A) showing a maximal peak in the enrichment signal corresponding to the expanded HNSC–Coad signature.
Genome view of the sequential consistency signatures used in the enrichment analysis of (A–C). The locations of consistently amplified glycolysis genes, canonical oncogenes, and tumor suppressors are indicated. Genes listed in parentheses (i.e., RPIA, TERC, TERT, APC, and TP53) were consistently altered across the human tumors but not consistently altered in the mouse models, due in part to the inclusion of p53 genetic knockout mouse models (TP53) and known differences in human and mouse telomere maintenance (TERC, TERT) (Sherr & DePinho, 2000). The synteny graph at the bottom indicates the syntenic mouse chromosome number and thus the broken synteny regions between human and mouse genomes. This genome view chronicles how the sequential pan‐cancer and cross‐species analysis of conserved amplification and deletion loci greatly reduces the percentage of consistent copy number alterations, thereby reducing the percentage of the genome implicated as candidate driver regions.
A. PC1‐sorted copy number profiles of a balanced, random sampling of tumors from the four core CNA‐consistent tumor types (breast, lung squamous, ovarian, and uterine carcinomas, Fig 1A) along with copy number profiles from primary breast carcinoma tumors with glycolytic levels imaged in vivo by 18F‐fluorodeoxy‐glucose positron emission tomography (FDG‐PET) (Palaskas et al, 2011). On the right, red and green values indicate high and low FDG standardized uptake values (SUVs), respectively, for FDG‐imaged tumors.
B. FDG uptake values in FDG‐PET measured tumors are highly correlated with CNA signature A PC1 score (ρ, Pearson rho correlation; P‐value = 5.3 × 10−5).
C. CNA values for genes from glycolysis and pentose phosphate pathways have stronger predictive power of FDG‐PET SUV in breast tumors and of lactate secretion (sec.) in breast cancer cell lines than other metabolism pathway‐based sets of genes. The table indicates the correlation between weighted gene voting (WGV)‐based predictions on the test sets and the measured metabolic phenotypes. WGV was performed with individual training on signature A tumors from each of the core four tumor types (breast (BRCA), lung (LU), ovarian (OV), and uterine (UCEC); top 10% signature A compared to normal (non‐tumor) samples), the voting predictions were averaged, and compared to the measured metabolic phenotype. P‐values were assessed by permutation analysis. See Table EV4 for all pathways.
D, E Signature A‐based WGV predictions and signature A‐based PC1 projections (as in B) have stronger correlation with measured lactate secretion for basal‐like breast cancer cell lines than for luminal‐like lines (D). See Appendix Fig S4B for luminal cell line data. Basal and luminal subtype classifications are from a published gene expression‐based determination (Neve et al, 2006). The breast cancer‐based glycolysis and pentose phosphate pathway (G & PP) WGV predictions are shown as a representative case (E).
A. KEGG metabolism pathway enrichment analysis based on mRNA expression in BRCA and LU signature A and signature B tumors. RNA expression data are from BRCA and LU tumors with paired TCGA DNA and RNA data. To evaluate the similarity to BRCA tumors with high FDG‐PET uptake, we included a gene set consisting of genes from the glycolysis and pentose phosphate pathway that were upregulated in FDG‐high BRCA tumors (Palaskas et al, 2011). To combine BRCA and LU into one enrichment analysis, genes were ordered by their average rank in BRCA and LU tumor types. Enrichment scores for all KEGG metabolism pathways and for individual tumor types can be found in Table EV4.
B–D RNA expression signatures of high glycolysis (Palaskas et al, 2011) were used to predict the glycolytic phenotype of BRCA (B), LU (C), and OV (D) tumors with paired TCGA DNA and RNA data. UCEC tumors were excluded due to a lack of sufficient samples with paired RNA and DNA data. The color scale was normalized for each tumor type by the mean FDG score for tumors with integrated CNA score > 0.2. Non‐normalized values are shown in the color legend and in (E).
E. RNA‐based WGV predictions of glycolysis show that BRCA and LU signature A tumors (top 10% PC1) are predicted to be more glycolytic than the tissue type‐matched signature B tumors (bottom 10% PC1). Mann–Whitney U‐test P‐values are shown. Data are presented in box (median, first and third quartiles) and whisker (extreme value) plots.
F. Spearman correlation values between RNA‐based WGV glycolysis predictions and CNA‐based PC1 values, calculated for different range windows of integrated CNA levels to control for the general increase in glycolysis predictions at increased levels of genomic instability. P‐values shown are calculated by performing 1 × 106 permutations where the WGV scores were randomly shuffled, and the P‐value was calculated as the percentage of random permutations that achieved a higher correlation value for any range window than did the experimentally observed relationship.
Top: Copy number profiles of 59 samples from 42 independent mouse embryonic fibroblasts (MEF) sublines before, during, and after senescence recapitulate the two‐signature CNA patterns observed in human tumors. Twenty‐two sublines evolved to Sig. A patterns, 13 sublines exhibited Sig. B, and seven sublines remained diploid‐like due to redox protection. PC1 scores for analysis of only signature A MEFs (PC1‐Sig A), only signature B MEFs (PC1‐Sig B), or all MEFs (PC1‐Sig AB) are indicated on the left. Also indicated are a metric of the degree of senescence observed during immortalization (senescence score), protection by 3% O2‐based hypoxia or catalase (+), or both (++) during immortalization, CNA profiling at passage 1 (P1), exogenous MYC expression (which enabled cells to bypass senescence), and Trp53 sequencing status (* indicates a non‐severe mutation p.183D > E, blank indicates not sequenced, additional p53 sequencing information in Appendix Table S1). Signature A MEF lines profiled at more than one passage number are indicated by the start (earlier passage) and end points (later passage) of the upward "evolving signature A" arrows. For comparison to (C), the early (25) and late (49) passages of the H1 subline that were characterized by spectral karyotyping (SKY) are indicated on the left by triangles. The indicated chromosome 6 region includes loci for Bpgm, Hk2, Rpia, Eno2, Tpi1, Gapdh, Tigar, Ldhb, and Kras. Bottom: Summary signatures of amplification and deletion loci in copy number profiles (normalized PC1 loadings) are shown for MEF WT and p53−/− signature A (Sig. A) samples. A paired t‐test analysis of signature A MEF lines profiled at more than one passage number revealed genomic regions associated with mid‐ to late‐passage CNA evolution (log10 t‐test P‐value signed positive for amplifications, negative for deletions; labeled "Evolving"). Individual profiles of p53−/− signature A samples are not shown.
Signature A MEFs have more DNA breakpoints and a larger degree of copy number alteration (integrated CNA score) than signature B MEFs. Signature A MEFs had a subset of cases with large numbers of breakpoints per chromosome (> 10) that were not observed in the signature B MEFs (hypergeometric P‐value = 0.02, Student's t‐test P‐value = 4 × 10−5). Data are presented in box (median, first and third quartiles) and whisker (extreme value) plots.
Spectral karyotyping (SKY) of the H1 MEF subline at passage 48. Whole chromosomal gains of varying extent are observed for all chromosomes with some chromosomes experiencing translocation, for example, t(3:16), and deletion, for example, del(4). Additional chromosome spreads and a summary table for P25 and P48 karyotypes are shown in Appendix Fig S8. CGH profiles for H1 cells are in (A) (indicated by the triangles in the SKY column) and Appendix Fig S6A and B.
The amount of senescence demonstrated during MEF line derivation (senescence score, see Materials and Methods) is highly correlated with the degree of copy number alterations obtained (integrated CNA score) (Spearman rho = 0.66, P‐value = 3 × 10−8). Single protection indicates protection by 3% O2 culture conditions or media supplementation with 250 U/ml catalase. Double protection indicates that cells were cultured at 3% O2 with catalase.
Conserved amplification and deletion loci in copy number profiles across core and expanded signature A human tumor types (Hs Sig. A), corresponding mouse tumorigenesis model signatures (Mm models), and the MEF immortalization system (MEF Sig. A). The human and mouse signatures are as defined in Fig 2, and the wild‐type MEF signatures are from (A). In the human consistent regions, the 52.3% consistently altered gene loci include bona fide tumor suppressor genes (p53), oncogenes (MYC, KRAS), telomere components (TERC, TERT), and core glycolysis genes (e.g., HK2). As in Fig 2D, genes listed in parentheses were consistently altered across the human tumors but not consistently altered in the mouse. The tissue‐specific, non‐lymphoid oncogenes from the COSMIC database that are in a conserved amplification or deletion region (TRRAP, CHD4) are listed for completeness (Forbes et al, 2015).
Enrichment signal strength (negative of log permutation P‐value) for the glycolysis and core glycolysis gene sets improve when MEF CNA signatures are added to the human and mouse CNA signatures from Fig 2. The degree of increased enrichment upon addition of the MEF signatures is quantitatively similar to adding mouse tumorigenesis model signatures. Adding all signatures into the analysis further strengthens the enrichment (last column). Table EV2 lists results for the enrichment analysis of the remaining MSigDB canonical pathways when human core and expanded signature A, mouse models, and MEF immortalization models are sequentially combined.
A. CD1 MEFs expressing exogenous HK1/HK2 or ENO2 exhibit reduced amplification of the endogenous Hk2 or Eno2 loci, respectively. Chr. 6 copy number profiles from control signature A MEFs (untransduced or expressing red fluorescent protein (RFP)) compared to signature A MEFs expressing either wild‐type HK1 or HK2, kinase‐dead HK2 (HK2 KD, D209A/D657A), or wild‐type ENO2. The positions of endogenous Hk2 and Eno2 are indicated. MEF lines profiled at more than one passage number are indicated by the start (earlier passage) and end points (later passage) of the arrows under "Evolving MEFs".
B–D Boxplots of Hk2 copy number (B), ratio of Hk2 copy number to maximum amplification of chromosome 6 (defined operationally as the 5th percentile CNA value across chr. 6 to avoid outlier effects) (C), and Eno2 copy number (D). Control MEFs: untransduced (squares) or expressing RFP (diamonds); test MEFs expressing wild‐type HK1 (upside‐down triangles), HK2 (triangles in B and C), kinase‐dead HK2 (HK2 KD, D209A/D657A, circles), or wild‐type ENO2 (triangle in D). In this analysis, copy number data from samples profiled at multiple passages were averaged to prevent overrepresentation of these cell lines. P‐values were calculated using Student's t‐test (B), Mann–Whitney U‐test (C), and z‐score (B, C) based on criteria described in Materials and Methods. Data are presented in box (median, first and third quartiles) and whisker (extreme value) plots.
E. Signature B MEFs expressing exogenous HK2 exhibit less amplification of the Hk1 locus. Chr. 10 copy number profiles from control signature B MEFs (untransduced or expressing RFP) compared to signature B MEFs expressing wild‐type HK2 or kinase‐dead HK2 (HK2 KD). The positions of endogenous Hk1 and Mdm2 are indicated.
F. Boxplot of the Hk1 copy number with indicated P‐value (z‐score). Data are presented in box (median, first and third quartiles) and whisker (extreme value) plots.
PCA‐defined signature A MEFs exhibit higher glucose consumption rates than signature B MEFs (Student's t‐test P‐value = 0.009). Glucose consumption was measured using a bioanalyzer.
PC1 scores of signature A MEFs are predictive of glucose consumption rates in signature A MEFs, while scores from signature B MEFs have weaker predictive power in signature B MEFs. In cross‐prediction tests, signature A‐based predictions of signature A MEF line metabolic phenotypes perform the best (Fig EV5A). Glucose consumption was measured using a bioanalyzer.
PCA‐defined signature A MEFs exhibit higher average growth fold change, as observed in 3T9 culture, compared to signature B MEFs. Signature A MEFs had a subset of cases with high growth rates (average fold change in cell number per passage > 4) that were not observed in the signature B MEFs (hypergeometric P‐value = 0.02).
Correlation and a general coevolution of higher growth rates and increased CNA signature strength. Arrowed lines indicate progressing MEF lines profiled at more than one passage number (Appendix Figs S6A and B, and S9A). In cross‐prediction tests, PC1 scores of signature A MEFs are more predictive of average growth fold change in signature A MEFs, while scores from signature B MEFs are more predictive in signature B MEFs (Fig EV5B).
Metabolomic profiling of 11 wild‐type MEF lines representative of either signature A or B cultured for 24 h with [1,2‐13C]‐labeled glucose. The metabolic pathway schematic is colored based on differences observed in the percent heavy label for intracellular metabolites (defined as percent of metabolite molecules with isotopomer mass greater than the monoisotopic molecular weight, M0) between signature A and B MEFs using the signal‐to‐noise (SNR) metric. Red indicates a higher heavy carbon‐labeling percentage in signature A MEFs, and blue indicates a higher heavy carbon‐labeling percentage in signature B MEFs. Signature A MEF lines incorporate more glucose‐derived carbon in metabolites from the early glycolysis steps, the pentose phosphate pathway, and nucleotide synthesis, and a smaller fraction of glucose‐derived carbon per molecule in metabolites from the later glycolysis steps, the serine synthesis pathway, and the TCA cycle. Full metabolomic data can be found in Table EV5.
Correlation of fructose‐1,6‐bisphosphate (F1,6BP) and negative correlation of 3‐phosphoserine (pSer) with glucose consumption rates. Note, the high to low range for percent metabolite molecules with incorporated label varies for each metabolite, but generally does not extend from 0 to 100%. Signature A and B MEFs are colored red and blue, respectively.
Model of copy number selection and fitness gains during tumorigenesis. Genomic instability enables fitness gains in tumor metabolism. In human tumors, cancer cell lines, and an experimental MEF immortalization system, immortalization and tumorigenesis lead to multiple CNA signatures that are predictive of the tumor phenotypes of metabolism and proliferation. Senescence‐associated redox stress and other tumorigenesis‐related constraints select for stronger CNA signatures. A shared high glycolysis‐associated signature A is observed in breast, lung, ovarian, and uterine tumors, additional tumor types, mouse models, and the MEF model system, and is linked with a higher range of glycolysis and proliferation phenotypes. Genetic manipulation of glycolysis enzymes leads to alteration of corresponding CNA signature propensities. Signature A and B genomes reflect two distinct trajectories from diploidy to tumor aneuploidy. Signature A tumors are enriched for mutations in p53 and have smaller sized amplification and deletion genomic regions (i.e., have a higher number of genomic breakpoints), potentially providing increased alternative genome options. Signature A involves amplification of several genes in glycolysis‐related pathways (such as HK2, TIGAR, TPI1, GAPDH, ENO2, PGAM2, and LDHB). Signature B CNA patterns occur in generally less glycolytic and proliferative samples and show more variation across different tumor types. In particular, signature B is enriched for MDM2 amplification and CDKN2A loss, strong MYC amplification, and KRAS mutation and involves alternate hexokinase isoforms (HK1, HK3).
A. In cross‐prediction tests, signature A‐based predictions of signature A MEF line metabolic phenotypes perform better than signature B‐based predictions. Glucose consumption was measured using a bioanalyzer.
B. In cross‐prediction tests, PC1 scores of signature A MEFs are more predictive of average growth fold change in signature A MEFs, while scores from signature B MEFs are more predictive in signature B MEFs.
C–G Mass spectrometry‐based metabolite measurements. Samples are arranged left to right from the strongest signature B (blue) PC1 scores to the strongest signature A PC1 (red) scores. Sample D10 (purple) is a mixed signature A/B line. (C) Relative intracellular metabolite levels. (D) Isotopomer distributions for intracellular metabolites (M0, monoisotopic molecular weight). (E) Percent label for intracellular metabolites defined as percent of metabolite molecules with isotopomer mass greater than the monoisotopic molecular weight. Note, the high to low range for percent metabolite molecules with incorporated label varies for each metabolite and generally does not extend from 0 to 100%. (F) Relative metabolite consumption from and secretion into media normalized to initial media levels (i.e., cellular metabolite footprint). Here, positive and negative values indicate metabolite secretion into and consumption from the media, respectively. In (D–G), the correlation of each metabolic parameter with glucose consumption (as measured by a bioanalyzer, and as a positive variable, Fig 6A) is indicated (Pearson correlation, ρ). In the isotopomer cases (D), the summary metric of percent label is used for the correlation determination. Notably, cells with high glucose consumption rates tend to exhibit high consumption of serine, glycine, and glutamine; and high secretion of lactate (with concordant lactate secretion results obtained by bioanalyzer‐based measurement of the same spent cell culture media). (G) Pathway schematics of differences in relative media levels (footprint, from F) between signature A and signature B MEFs. Each node is colored according the signal‐to‐noise (SNR) ratio. Red indicates higher post‐culture media levels (lower consumption or higher secretion rates) in signature A MEFs, and blue indicates higher post‐culture media levels in signature B MEFs. Error bars indicate standard deviations of biological replicates. Footprinting data were normalized to the integrated cell number of the time course of labeling (24 h), and intracellular metabolite concentrations were normalized to the number of cells present at the time of extraction. Full metabolomic data can be found in Table EV5.
Appendix [msb167159-sup-0001-Appendix.pdf]
Expanded View Figures PDF [msb167159-sup-0002-EVFigs.pdf]
Table EV1 [msb167159-sup-0003-TableEV1.xlsx]
Table EV2 [msb167159-sup-0004-TableEV2.xlsx]
Table EV3 [msb167159-sup-0005-TableEV3.xlsx]
Table EV4 [msb167159-sup-0006-TableEV4.xlsx]
Table EV5 [msb167159-sup-0007-TableEV5.xlsx]
Review Process
Request Permissions


text:
As you can see Websaver Is giving their website a Face lift and updating their site. There is now a section for just Printable Coupons and its up and running.
They also have a new spot for Mail to you coupons and they are calling it the VIP Club. its still being worked on but we will know what is all about within the next few days stay tuned.
Make sure your Java is updated for for Printing off coupons.
Mailable coupons are now live also so order yours now.
Click Here to check out the new updated format of the Printable coupons and site.


text:
The worst investment in sports fandom is the NFL jersey.
Take, for example, Peyton Manning. There's no guarantee he'll be back in 2016.
But Broncos supporters have nothing on San Diego and Oakland fans. At least they know they'll have a team next year.
Both the Chargers and Raiders are considering a move to Los Angeles, a disruptive scenario that could derail a season. Ask the 1995 Cleveland Browns, who lost 10 of their last 12 and got Bill Belichick fired when news of their imminent move to Baltimore went public.
With that volatile backdrop, the AFC West appears to be wide open, with the Broncos, Chargers and Chiefs all holding a reasonable shot at winning the division.
A hard-to-believe parting stat: The last time an AFC West team won it all was Super Bowl XXXIII — John Elway's final game as a player. The 17-year drought is the longest of any division in football.
▪ 2014 record: 12-4 (first in AFC West).
▪ Coach: Gary Kubiak (first season).
▪ Training camp report date: Rookies reported Monday, veterans report Thursday (Paul D. Bowlen Memorial Broncos Centre; Englewood, Colorado).
▪ Major additions: TE Owen Daniels, DE Shane Ray, S Darian Stewart.
▪ Key losses: DT Terrance Knighton, S Rahim Moore, TE Julius Thomas.
▪ Outlook: Has Denver's window closed? Peyton Manning turned 39 this year, and his durability is a real concern. Manning was awful down the stretch and in Denver's playoff game last season, the result of a torn right quadriceps. And with left tackle Ryan Clady lost for the season with a ruptured ACL, the offensive line could be an issue. The good news: Denver's defense, which was second in the NFL in yards per play allowed last year (4.8), should be just as good, if not better. Grabbing Shane Ray with the 23rd pick in the NFL Draft could end up a steal.
▪ 2014 record: 9-7 (t-second in AFC West).
▪ Coach: Andy Reid (third season).
▪ Training camp report date: Rookies reported Tuesday, veterans report Friday (Missouri Western State University; St. Joseph, Missouri).
▪ Major additions: S Tyvon Branch, WR Jeremy Maclin, CB Marcus Peters.
▪ Key losses: WR Dwayne Bowe, TE Anthony Fasano, G Rodney Hudson.
▪ Outlook: Only four AFC teams have done better than the Chiefs' 20-12 mark over the past two seasons. That's a credit to both Andy Reid and Alex Smith, who are a perfect fit. And with defensive end Justin Houston locked up for the next six years, the defense will be no slouch, either. But there's a gulf of difference between competitive and championship caliber. The Chiefs' limitations are well-documented. They were the first team in 40 years to go the entire season without a having a receiver catch a touchdown pass. Kansas City replaced Dwayne Bowe with Jeremy Maclin in an effort to change that.
▪ 2014 record: 3-13 (fourth in AFC West).
▪ Coach: Jack Del Rio (first season).
▪ Training camp report date: Rookies reported Sunday, veterans report Thursday (Napa Valley Marriott; Napa, California).
▪ Major additions: WR Amari Cooper, G Rodney Hudson, LB Malcolm Smith.
▪ Key losses: RB Darren McFadden, DT Pat Sims, C Stefan Wisniewski.
▪ Outlook: Is there finally a light at the end of the tunnel for the Raiders, who have been the league's laughingstock for a decade? Jack Del Rio brings credibility to an organization that hasn't had much of any since Jon Gruden left for Tampa Bay a generation ago. Armed with $50 million in salary-cap space, Oakland used it on a bunch of B to B-plus players — but only after striking out with the big fish. That might have been a disguised blessing, however. The Raiders' turnaround will come through the draft, and many believe they hit a home run with Amari Cooper, the Bama burner out of Miami Northwestern.
▪ 2014 record: 9-7 (t-second in AFC West).
▪ Coach: Mike McCoy (third season).
▪ Training camp report date: Wednesday (Chargers Park; San Diego).
▪ Major additions: G Orlando Franklin, RB Melvin Gordon, WR Stevie Johnson.
▪ Key losses: LB Jarret Johnson, RB Ryan Mathews, WR Eddie Royal.
▪ Outlook: Give the Chargers this: They knew their weakness and attacked it aggressively. San Diego was one of the worst rushing teams in football last year, ranking 31st in yards per rush (3.4) and 30th in rushing yards (85.4). The Chargers signed free agent linemen Orlando Franklin (University of Miami) and Joe Barksdale, brought back tackle King Dunlap, and most importantly, selected running back Melvin Gordon in the first round. Keep an eye on versatile Jimmy Wilson, the former Dolphins defensive back who signed with his hometown team this offseason.


text:
Hanging on by a thread
Weemsy and Floflo are middle Pinellas county's premier internet comedy team. The duo has produced such classics as their best selling muzak album "A Cacophony of Turds", their short film "Hey... Who Farted?", the self help book "Men are from Mars, and Women are Bitches", the workout video series "Jogging to Your Car With Weemsy", and the unforgetable mini series "Like A Feather to the Scrote".


text:
A journey of a thousand miles begins with a single step – Lao-Tzu (604 BC – 531 BC)
Large enterprise or a small / medium business or just a startup (funded or otherwise), India's sought after inbound marketing company is always excited to solve customer acquisition problems.
Please tell us your requirements and our super team would revert to you in 4 hours.
Email : firstname.lastname@example.com
Contact : +91-9717240021
B1, 259, Spaze iTech Park
Sector 49, Gurugram - 122018 (India)


text:
Last updated Wednesday, December 14, 2016
The delegates to the USCA from the various regions and from qualifying Affiliated Clubs (the "Board") meet twice a year to deliberate and decide on the administration and management of the USCA.
The Annual Meeting is held, typically, on the second full weekend of January, at a location voted on by the Board at the previous year's Annual Meeting from bids presented by aspiring hosts. The 2017 Annual Meeting will be held January 13-15, in Charlotte, NC. For information on this meeting, go to 2017 USCA Annual Meeting
SemiAnnual Meetings are held on the Friday evening of Nationals week and are hosted by the Nationals host.
Would you and/or your local club/division like to host the 2018 USCA Annual Meeting?
Dates for the 2018 Annual Meeting are set for Friday through Sunday, January 12-14, 2018.
Delegates to the USCA will vote on bids at the 2017 Annual Meeting in Charlotte, NC, January 13-15, 2017.
Anyone may make a bid. However, because a number of volunteers are required (see Guide to Hosting, below) both before and during the meeting, bids from paddling clubs (especially USCA Affiliated Clubs or USCA Divisions) or other organized groups with willing volunteers may be preferred.
Those interested in hosting this meeting should consult the documents linked below. It would be a good idea to let the Annual Meeting Coordinator, currently Larry Latta
Deadline for bids to be received, midnight EST, Sunday December 1, 2016:
The deadline for bids to be received (by Larry Latta, the Annual Meeting Coordinator) is midnight EST, Sunday December 1, 2016. Incomplete bids or bids received by the Annual Meeting Coordinator after the deadline will neither be accepted nor presented. The bid deadline will only be extended in the event that (a) no complete bids have been received by the deadline or (b) a request for, at most, a four-day extension due to extenuating circumstances has been received by the December 1 deadline, and granted.
A complete bid must be delivered in writing, electronically by email with attachments, to firstname.lastname@example.com, copy to the USCA Webmaster, and must provide the information listed in the document How to Make a Bid to Host the January 2018 USCA Annual Meeting, including details about hotel and meeting rooms, airport and shuttle details, meals (including banquet), and a commitment to fulfill the requirements outlined in A Guide to Hosting an Annual Meeting for the USCA.
Verbal bids, incomplete bids, or bids not received in electronic form will not be accepted.
Please refer to the following documents, which may be found at USCA's documents page:
1. Direct download here: How to Make a Bid to Host the January 2018 USCA Annual Meeting
2. Direct download here: A Guide to Hosting an Annual Meeting for the USCA
Larry Latta (VP-USCA)
Annual Meeting Coordinator
United States Canoe Association
1188 Broken Bow Court
Westerville, OH 43081-3262
Further advice can be sought from, or questions answered by, the